Climbing Mount Probable

2021 ◽  
pp. 135-164
Author(s):  
Arlin Stoltzfus
Keyword(s):  
Modern Synthesis ◽  
Causal Process ◽  
Gene Frequencies ◽  
Formal Basis ◽  
One Step ◽  
Adaptive Walks ◽  
Per Se ◽  
New Mutations

Chapter 8 provides the formal basis to recognize biases in the introduction of variation as a cause of evolutionary biases. The shifting-gene-frequencies theory of the Modern Synthesis posits a “buffet” view in which evolution is merely a process of shifting the frequencies of pre-existing alleles, without new mutations. Within this theory, mutation is represented like selection or drift, as a “force” that shifts frequencies. Yet, within a broader conception of evolution, a second kind of causal process is required: an introduction process that can shift a frequency upwards from 0, which selection and drift cannot do. Abstract models demonstrate the influence of biases in the introduction process in one-step and multi-step adaptive walks. Such biases do not require mutation biases per se, but may arise from effects of development, and from the differential accessibility of alternative forms in abstract possibility-spaces.

Study of a mechanism responsible for anomalous results for free thyroxin by some analog assays for subjects with albumin deficiency.

1984 ◽  
Vol 30 (11) ◽  
pp. 1742-1745 ◽  
Author(s):  
T J Wilke
Keyword(s):  
Single Step ◽  
Nonthyroidal Illness ◽  
One Step ◽  
The Mean ◽  
Per Se ◽  
In Pregnancy ◽  
Deficient Group

Abstract I examined the effect of albumin deficiency, as might occur in pregnancy and nonthyroidal illness, on four analog-based assays for free thyroxin (Amersham's Amerlex, Diagnostic Products Corporation's Coat-A-Count "one-step," Clinical Assays' Gammacoat "one-step," and Corning's Immophase "single-step"). In subjects with albumin deficiency per se, Amerlex and Coat-A-Count results for free thyroxin were not significantly different from normal, whereas free thyroxin values by Gammacoat and Immophase assays were lower than that of the control. Furthermore, in the albumin-deficient group, the mean amount of thyroxin associated with antisera in each assay was significantly higher than that of the control and correlated well with the degree of decrease in free thyroxin. I conclude that subnormal results for thyroxin by analog assays, in euthyroid patients with albumin deficiency, is a function of the specific assays and is not a characteristic of analog assays per se. In addition, the study suggests that albumin deficiency alters the distribution between thyroxin and its binders in all four analog assays, but only in the Gammacoat and Immophase methods is this alteration sufficiently large as to distort assay results.

Resilience and measured gene–environment interactions

2012 ◽  
Vol 24 (4) ◽  
pp. 1297-1306 ◽  
Author(s):  
Julia Kim-Cohen ◽  
Rebecca Turkewitz
Keyword(s):  
Mental Disorders ◽  
Childhood Maltreatment ◽  
Developmental Psychopathology ◽  
Environmental Risks ◽  
Causal Process ◽  
Environmental Stressor ◽  
Positive Adaptation ◽  
The Past ◽  
Gene Environment ◽  
One Step

AbstractThe past decade has witnessed an exponential growth in studies that have attempted to identify the genetic polymporphisms that moderate the influence of environmental risks on mental disorders. What tends to be neglected in these Gene × Environment (G × E) interaction studies has been a focus on resilience, which refers to a dynamic pattern of positive adaptation despite the experience of a significant trauma or adversity. In this article, we argue that one step toward advancing the field of developmental psychopathology would be for G × E research to consider resilience instead of focusing almost exclusively on mental disorders. After providing an up-to-date summary on the expanding definitions and models of resilience, and the available evidence regarding measured G × E studies of childhood maltreatment, we discuss why resilience would be a worthwhile phenotype for studies of measured G × E. First, although G × E hypotheses require that there be an environmental risk (e-risk) involved in a causal process that leads to psychopathology, e-risks are typically not included in the diagnostic criteria for most psychiatric disorders. In contrast, resilience by definition includes an e-risk. Second, G × E hypotheses require that there is evidence of variability in response to an environmental stressor, and resilience often represents the positive end on this continuum of adaptation. Third, both resilience and G × E are best understood from a developmental perspective. Fourth, although resilient outcomes are not public health concerns, the types of adversities (e.g., childhood maltreatment, poverty, or exposure to natural disasters) that are often investigated in studies of resilience certainly are. Understanding how some individuals, perhaps because of their genetic makeup, are able to withstand such adversities can inform prevention and intervention efforts to improve mental health.

scholarly journals A Bayesian MCMC Approach to Assess the Complete Distribution of Fitness Effects of New Mutations: Uncovering the Potential for Adaptive Walks in Challenging Environments

Genetics ◽  
2014 ◽  
Vol 196 (3) ◽  
pp. 841-852 ◽  
Author(s):  
Claudia Bank ◽  
Ryan T. Hietpas ◽  
Alex Wong ◽  
Daniel N. Bolon ◽  
Jeffrey D. Jensen
Keyword(s):  
Bayesian Mcmc ◽  
Fitness Effects ◽  
Adaptive Walks ◽  
Mcmc Approach ◽  
New Mutations

Introduction: a curious disconnect

2021 ◽  
pp. 1-14
Author(s):  
Arlin Stoltzfus
Keyword(s):  
Molecular Evolution ◽  
Population Genetic ◽  
Modern Synthesis ◽  
Self Organization ◽  
Gene Frequencies ◽  
Major Topic ◽  
Central Argument ◽  
Evo Devo

Chapter 1 begins with a synopsis of the central argument concerning models of evolution (and theories of causation) that incorporate a mutational introduction process, using a study of laboratory adaptation that shows proportional effects of a 50-fold range of rates for different mutations. The exploration of the role of variation in this book covers mutation and randomness, the neo-Darwinian dichotomy of selection and variation, the shifting-gene-frequencies theory of the Modern Synthesis (and its relation to population-genetic “forces“), developmental bias, self-organization, the emergence of evolvability as a major topic, and the causes of parallel adaptation. This chapter provides a guide to the remainder of the book, and explains how the main arguments relate to more familiar topics such as evo-devo, the distinctiveness of molecular evolution, the “directed mutations“ controversy, and debates about the adequacy of a “Modern Synthesis.”

Origin of Hepatic Nuclear Inclusion Bodies

1973 ◽  
Vol 31 ◽  
pp. 426-427
Author(s):  
F. G. Zaki ◽  
J. A. Greenlee ◽  
C. H. Keysser
Keyword(s):  
Inclusion Bodies ◽  
Storage Disease ◽  
Glycogen Storage ◽  
Nutritional Deficiencies ◽  
Nuclear Inclusion ◽  
Electron Microscopic ◽  
Human Liver Cells ◽  
Microscopic Studies ◽  
Per Se ◽  
Experimental Liver

Nuclear inclusion bodies seen in human liver cells may appear in light microscopy as deposits of fat or glycogen resulting from various diseases such as diabetes, hepatitis, cholestasis or glycogen storage disease. These deposits have been also encountered in experimental liver injury and in our animals subjected to nutritional deficiencies, drug intoxication and hepatocarcinogens. Sometimes these deposits fail to demonstrate the presence of fat or glycogen and show PAS negative reaction. Such deposits are considered as viral products.Electron microscopic studies of these nuclei revealed that such inclusion bodies were not products of the nucleus per se but were mere segments of endoplasmic reticulum trapped inside invaginating nuclei (Fig. 1-3).

An Interactive Minicomputer Program for the Indexing and Simulation of Electron Diffraction Patterns

1976 ◽  
Vol 34 ◽  
pp. 542-543
Author(s):  
R.P. Goehner ◽  
W.T. Hatfield ◽  
Prakash Rao
Keyword(s):  
Electron Diffraction ◽  
Real Time ◽  
Pattern Analysis ◽  
Flow Diagram ◽  
Hard Copy ◽  
Time Analysis ◽  
Real Time Analysis ◽  
Transmission Electron ◽  
One Step ◽  
Diffraction Patterns

Computer programs are now available in various laboratories for the indexing and simulation of transmission electron diffraction patterns. Although these programs address themselves to the solution of various aspects of the indexing and simulation process, the ultimate goal is to perform real time diffraction pattern analysis directly off of the imaging screen of the transmission electron microscope. The program to be described in this paper represents one step prior to real time analysis. It involves the combination of two programs, described in an earlier paper(l), into a single program for use on an interactive basis with a minicomputer. In our case, the minicomputer is an INTERDATA 70 equipped with a Tektronix 4010-1 graphical display terminal and hard copy unit.A simplified flow diagram of the combined program, written in Fortran IV, is shown in Figure 1. It consists of two programs INDEX and TEDP which index and simulate electron diffraction patterns respectively. The user has the option of choosing either the indexing or simulating aspects of the combined program.

The Eleventh Circuit Holds that Agreements in which Pharmaceutical Companies Pay Generic Companies Not to Compete May be Valid

2004 ◽  
Vol 32 (1) ◽  
pp. 181-184
Author(s):  
Amy Garrigues
Keyword(s):  
Pharmaceutical Companies ◽  
Court Decisions ◽  
Patent Holder ◽  
Trial Court ◽  
Court Of Appeals ◽  
The Us ◽  
Antitrust Laws ◽  
Per Se ◽  
Appeals Court ◽  
Two Sides

On September 15, 2003, the US. Court of Appeals for the Eleventh Circuit held that agreements between pharmaceutical and generic companies not to compete are not per se unlawful if these agreements do not expand the existing exclusionary right of a patent. The Valley DrugCo.v.Geneva Pharmaceuticals decision emphasizes that the nature of a patent gives the patent holder exclusive rights, and if an agreement merely confirms that exclusivity, then it is not per se unlawful. With this holding, the appeals court reversed the decision of the trial court, which held that agreements under which competitors are paid to stay out of the market are per se violations of the antitrust laws. An examination of the Valley Drugtrial and appeals court decisions sheds light on the two sides of an emerging legal debate concerning the validity of pay-not-to-compete agreements, and more broadly, on the appropriate balance between the seemingly competing interests of patent and antitrust laws.

Fusion and Fission Processes in Exocytosis: Possible Roles for Synexin and Osmotic Lysis in the Two Events

1980 ◽  
Vol 38 ◽  
pp. 594-597
Author(s):  
H.B. Pollard ◽  
C.E. Creutz ◽  
C.J. Pazoles ◽  
J.H. Scott
Keyword(s):  
Small Molecules ◽  
Chromaffin Cells ◽  
Adrenal Glands ◽  
General Concept ◽  
Extracellular Calcium ◽  
Large Protein ◽  
Granule Membrane ◽  
Osmotic Lysis ◽  
Per Se ◽  
Chemical Evidence

Exocytosis is a general concept describing secretion of enzymes, hormones and transmitters that are otherwise sequestered in intracellular granules. Chemical evidence for this concept was first gathered from studies on chromaffin cells in perfused adrenal glands, in which it was found that granule contents, including both large protein and small molecules such as adrenaline and ATP, were released together while the granule membrane was retained in the cell. A number of exhaustive reviews of this early work have been published and are summarized in Reference 1. The critical experiments demonstrating the importance of extracellular calcium for exocytosis per se were also first performed in this system (2,3), further indicating the substantial service given by chromaffin cells to those interested in secretory phenomena over the years.

Nutrient-regulated gene expression in eukaryotes

2006 ◽  
Vol 73 ◽  
pp. 85-96 ◽  
Author(s):  
Richard J. Reece ◽  
Laila Beynon ◽  
Stacey Holden ◽  
Amanda D. Hughes ◽  
Karine Rébora ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Control ◽  
Direct Interaction ◽  
Signalling Pathways ◽  
A Cell ◽  
One Step ◽  
Higher Eukaryotes ◽  
Regulated Gene Expression

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. In higher eukaryotes, the signalling pathway between metabolite recognition and transcriptional control can be complex. Recent evidence from the relatively simple eukaryote yeast suggests that complex signalling pathways may be circumvented through the direct interaction between individual metabolites and regulators of RNA polymerase II-mediated transcription. Biochemical and structural analyses are beginning to unravel these elegant genetic control elements.

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